{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:39:04Z","timestamp":1776278344720,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T00:00:00Z","timestamp":1645228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cenobamate is an antiseizure medication for uncontrolled focal seizures. This thorough QT study assessed the effects of therapeutic and supratherapeutic cenobamate doses (maximum recommended dose, 400\u00a0mg\/day) on correct QT interval (QTc) in healthy adults (N\u00a0=\u00a0108) randomly assigned to 1 of 3 treatments: (A) cenobamate (days 1\u201063) up\u2010titrated by 50\u2010mg increments weekly to a 200\u00a0mg\/day therapeutic dose (day 35) and then by 100\u00a0mg weekly to a 500\u00a0mg\/day supratherapeutic dose (day 63), with placebo\u2010moxifloxacin (days \u22121 and 64); (B) moxifloxacin 400\u00a0mg (day \u22121; positive control), placebo\u2010cenobamate (days 1\u201063), and placebo\u2010moxifloxacin (day 64); and (C) placebo\u2010moxifloxacin (day \u22121), placebo\u2010cenobamate (days 1\u201064), and moxifloxacin 400\u00a0mg (day 64). The primary end point was baseline\u2010adjusted, placebo\u2010corrected QTc (\u0394\u0394QTcF; corrected for heart rate [HR] by Fridericia's method) with cenobamate 200 and 500\u00a0mg\/day. Baseline electrocardiographic parameters were balanced across groups. Mean \u0394\u0394QTcF was negative throughout for cenobamate doses (largest: day 35, \u221210.8\u00a0milliseconds; day 63, \u221218.4\u00a0milliseconds). Based on concentration\u2010QTc analysis, \u2206\u2206QTcF effect was predicted as \u22129.85 and \u221217.14\u00a0milliseconds at mean peak plasma levels of therapeutic (200\u00a0mg\/day; 23.06\u00a0\u03bcg\/mL) and supratherapeutic (500\u00a0mg\/day; 63.96\u00a0\u03bcg\/mL) doses. Cenobamate had no clinically relevant prolonging effect on electrocardiographic parameters (eg, PR, QRS); HR effects were similar to placebo. Cenobamate showed slight dose\u2010related shortening of QTc, but to a degree not known to be clinically relevant (no reductions \u2264340\u00a0milliseconds). Cenobamate had no clinically relevant effects on HR or electrocardiographic parameters and no QTc\u2010prolonging effect at therapeutic\/supratherapeutic doses. Cenobamate is contraindicated in patients with short\u2010QT syndrome and caution should be used when coadministering with drugs that shorten QT interval.<\/jats:p>","DOI":"10.1002\/cpdd.1077","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T08:41:13Z","timestamp":1645260073000},"page":"523-534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Phase 1 Clinical Study Evaluating the Effects of Cenobamate on the QT Interval"],"prefix":"10.1002","volume":"11","author":[{"given":"Borje","family":"Darpo","sequence":"first","affiliation":[{"name":"Clario  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip T.","family":"Sager","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute and Department of Medicine Stanford University  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongqi","family":"Xue","sequence":"additional","affiliation":[{"name":"Clario  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Kamin","sequence":"additional","affiliation":[{"name":"SK Life Science, Inc.  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